X-9739333-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000273.3(GPR143):c.1120+152C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 486,303 control chromosomes in the GnomAD database, including 7,749 homozygotes. There are 26,793 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1238 hom., 4912 hem., cov: 23)
  • Exomes 𝑓: 0.17 (6511 hom. 21881 hem.)
• Consequence: GPR143 NM_000273.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.455

Genes affected

GPR143 (HGNC:20145): (G protein-coupled receptor 143) This gene encodes a protein that binds to heterotrimeric G proteins and is targeted to melanosomes in pigment cells. This protein is thought to be involved in intracellular signal transduction mechanisms. Mutations in this gene cause ocular albinism type 1, also referred to as Nettleship-Falls type ocular albinism, a severe visual disorder. A related pseudogene has been identified on chromosome Y. [provided by RefSeq, Dec 2009]

LOC105373126 (HGNC:):

TBL1X (HGNC:11585): (transducin beta like 1 X-linked) The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. The WD40 group is a large family of proteins, which appear to have a regulatory function. It is believed that the WD40 repeats mediate protein-protein interactions and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation. This encoded protein is found as a subunit in corepressor SMRT (silencing mediator for retinoid and thyroid receptors) complex along with histone deacetylase 3 protein. This gene is located adjacent to the ocular albinism gene and it is thought to be involved in the pathogenesis of the ocular albinism with late-onset sensorineural deafness phenotype. Four transcript variants encoding two different isoforms have been found for this gene. This gene is highly similar to the Y chromosome TBL1Y gene. [provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant X-9739333-G-A is Benign according to our data. Variant chrX-9739333-G-A is described in ClinVar as [Benign]. Clinvar id is 1238273.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR143	NM_000273.3	c.1120+152C>T		intron_variant		ENST00000467482.6
LOC105373126	XR_950507.2	n.1620+614G>A		intron_variant, non_coding_transcript_variant
GPR143	XM_005274541.4	c.1120+152C>T		intron_variant
GPR143	XM_024452388.2	c.868+152C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR143	ENST00000467482.6	c.1120+152C>T		intron_variant		1	NM_000273.3	P1
TBL1X	ENST00000647060.1	c.1555-1449G>A		intron_variant
GPR143	ENST00000487206.1	n.235+152C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 15989 AN: 111258 Hom.: 1231 Cov.: 23 AF XY: 0.147 AC XY: 4910 AN XY: 33472

Gnomad AFR AF: 0.0764

Gnomad AMI AF: 0.0539

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.175 AC: 65530 AN: 374990 Hom.: 6511 AF XY: 0.167 AC XY: 21881 AN XY: 131276

Gnomad4 AFR exome AF: 0.0783

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.628

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.144 AC: 15997 AN: 111313 Hom.: 1238 Cov.: 23 AF XY: 0.146 AC XY: 4912 AN XY: 33537

Gnomad4 AFR AF: 0.0764

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.172

Alfa AF: 0.125 Hom.: 1370

Bravo AF: 0.163

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.47
Dann	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11095519; hg19: chrX-9707373; COSMIC: COSV66632756; COSMIC: COSV66632756;